Samuel Barondes, Robertson Professor of Neurobiology and Psychiatry
at the University of California, San Francisco, is one of the
true pioneers in the field of ‘Molecular Psychiatry’. Barondes
is a member of the Institute of Medicine of the National Academy
of Sciences, President of the McKnight Endowment Fund for Neuroscience
and recently Chairman of a Workgroup on Genetics for the National
Institute of Mental Health and author of Mood Genes: Hunting
for Origins of Mania and Depression.

Manic-depression has afflicted some of the most creative minds,
Dickens, Byron, van Gogh, Schumann and Newton among them. This
very association gives the story an interesting subtext – many
‘patients’ either do not believe they are ill or do not wish treatment
(principally due to the enticement and energy of the manic phase).
Theoretical geneticists have inferred the genes have actually
been selected into the genome. Still, the costs are steep
and often entail appallingly bad or even dangerous judgments –
sexual indiscretions, fiscal calamities, family and work woes,
and even suicide.

The New York Times described his book as ”unputdownable” and
other reviews have likened it to a spy thriller. Pert words for
a science book, but I too found Mood Genes engrossing.
It is substantive yet highly readable, in large part due to the
clear language, coherent progression of subject and the avuncular
tone that Barondes maintains. One would hardly know he is himself
among the leaders in the field, amid all his clarity, affection
for the science, and personal modesty. Yet his team has persevered
in research with affected families in the United States and Costa
Rica.

The hunt for mood genes is significant and timely since, Barondes
notes, bipolar manic-depression affects "about one in a hundred
of us in its flagrant form, and possibly several times as many
of us in its milder version." Moreover, the long-standing
observation that mood disorders often run in families – often
imminent families – strongly suggests a basis in hereditary and
genetics. Hence, psychiatric geneticists are avidly studying DNA
samples in family lineages to identify genes and molecular mechanisms
characteristic of the disease. Such mechanisms will be the foundation
for more precise treatments in the future.

Barondes begins with a painlessly concise introduction to modern
genetics that specialists may readily pass over but it is worth
a read if only as an example of crisp writing. It generally achieve
avoids technical terms or otherwise clarifies what are ”centimorgans,”
”lod scores,” ”riflips” and such like.

But then the tale picks up speed.

In the course of the book’s 10 chapters, 193 text pages and an
exceptional set of notes, Barondes interweaves a peppy historiography
of recent, pivotal research with an explanation of the scientific
strategies and advanced technology by which genetic linkage analyses
proceed. Barondes invokes the metaphor of a screenplay in which
”the enemy spy with the secret radio transmitter is tracked down
by gradually homing in on the source of the radio waves.”

A typical method of mood-gene sleuthing is to identify a family
with a lot of mania and deprssion, then ascertain whether any
association with known genetic markers (DNA fragments with known
chromosomal loci). If so, this is a ‘hot lead’ that narrows the
search since it is likely a relevant gene is present nearby. The
trail is indeed ‘hot’, but the case is not closed. ‘Leads’ have
been found along the "long arm" of chromosome 18 as
well as chromosomes 4, 6, 13, and 15.

Of course, such searches for genes that affect behavior run the
gamut from schizophrenia, autism, Tourette’s syndrome, substance
abuse onto Alzheimer’s disease and beyond. Likewise, linkage analyses
are underway for almost every medical condition thought to have
a significant genetic basis. As Barondes says, "Over the
long run as genes that predispose people to specific mental disorders
are found, we will begin to understand that these are illnesses
like other kinds of physical illnesses and that some people are
especially vulnerable."

This progress in genomics already feeds a lively debate over ethical,
legal and social dimensions. But almost certainly, the identification
of genes linked to mood syndromes will give rise to new tests
and treatments. One sharp controversy is to do with the nigh-inevitability
of pre-natal testing and selective abortion. While some expectant
parents may understandably opt to terminate pregnancies at great
risk of carrying bipolar disorder, might such culling also deprive
such individuals and society as a whole of persons with extended
range of affect and ability? Novel medications may derive from
an increasing grasp on the proteins, enzymes, or hormones products
and/or how such products specialized molecules affect the brain
and mind. These eugenic concerns may be transcended if new medications
may render the disease harmless or even allow the manic tendency
to be effectively harnessed. Ever the optimist, Barondes is confident
the enhancement of treatment options will outweigh many of these
concerns.

If Mood Genes is a detective story, it is a cliff-hanger:
there is no clear ‘culprit’. That manic-depression is a robustly
genetic syndrome was documented rather early in the 20^th
Century. However, the elucidation of the more precise genetic
loci and effects of the syndromic DNA remain an object of ‘hot
pursuit’ even now in the early 21^st century.

© 2001 Daniel R. Wilson

Daniel R. Wilson, MD, Ph.D., Chairman
of the Department of Psychiatry and Professor of Psychiatry and
Anthropology.

Categories: Depression, Genetics

Tags: Bipolar Disorder, Depression (Unipolar)